A Phase l/ll Study of AMN107 in Adult Patients With Glivec-intolerant CML or Relapsed-refractory Ph+ALL

NCT ID: NCT00384228

Last Updated: 2020-12-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-05-31

Brief Summary

This study will investigate if nilotinib provides an improved safety and efficacy profile over that seen in patients receiving Imatinib.

Conditions

Chronic Myelogenous Leukemia; Acute Lymphoblastic Leukemia (Philadelphia Chromosome Positive)

Keywords

Chronic Myelogenous Leukemia; Acute Lymphoblastic Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nilotinib

Group Type: EXPERIMENTAL

Nilotinib

Intervention Type: DRUG

Interventions

Nilotinib

Intervention Type: DRUG

Other Intervention Names

AMN107

Eligibility Criteria

Inclusion Criteria

• Diagnosed as Ph+ ALL who are either relapsed after or refractory to standard therapy
• Diagnosed as CML in blast crisis or accelerated phase or chronic phase who are resistant or intolerant to imatinib

Exclusion Criteria

• A history of significant or serious uncontrolled cardiovascular disease
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of nilotinib
• Patients who are pregnant or breast feeding, or adults of reproductive potential not employing an effective method of birth control

• Cytopathologically confirmed CNS infiltration NB: in absence of suspicion of CNS involvement, lumbar puncture is not required
• Impaired cardiac function, including any one of the following

• LVEF < 45% as determined by echocardiogram
• Complete left bundle branch block
• Use of a cardiac pacemaker
• ST depression of > 1mm in 2 or more leads and/or T-wave inversions in 2 or more contiguous leads
• Congenital long QT syndrome
• History of or presence of significant ventricular or atrial tachyarrhythmias
• Clinically significant resting bradycardia (< 50 beats per minute)
• QTc > 480 msec on screening ECG (using the QTcF formula)
• Right bundle branch block plus left anterior hemiblock, bifascicular block
• Myocardial infarction within 3 months prior to starting AMN107
• Uncontrolled angina pectoris
• Other clinically significant heart disease (e.g., congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of AMN107 (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
• Use of therapeutic warfarin
• Acute or chronic liver or renal disease considered unrelated to tumor (e.g., hepatitis, cirrhosis, renal insufficiency, etc.)
• Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes, active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol
• Treatment with any hematopoietic colony-stimulating growth factors (e.g., G-CSF) ≤ 1 week prior to starting study drug.
• Patients who are currently receiving treatment with any of the medications listed in (cf. Post-text suppl. 5) that cannot be either discontinued or switched to a different medication prior to starting study drug. The medications listed in (cf. Post-text suppl. 5) have the potential to prolong the Q-T interval.
• Patients who have received chemotherapy ≤ 1 week or who are within 5 half-lives of their last dose chemotherapy (6 weeks for nitrosurea or mitomycin-C) prior to starting study drug or who have not recovered from side effects of such therapy. Hydroxyurea is permitted at the investigator's discretion prior to enrollment.
• Patients who have received Glivec® ≤ 1 week or who have not recovered from side effects of such therapy.
• Patients who have received immunotherapy ≤ 1 week prior to starting study drug or who have not recovered from side effects of such therapy.
• Patients who have received any investigational drug (excluding STI571/Glivec) ≤ 4 weeks or investigational cytotoxic agent within 1 week (or who are within 5 half-lives of a previous investigational cytotoxic agent) prior to starting study drug or who have not recovered from side effects of such therapy.
• Patients who have received wide field radiotherapy ≤ 4 week or limited field radiation for palliation ≤ 2 week prior to starting study drug or who have not recovered from side effects of such therapy.
• Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
• Patients who are pregnant or breast feeding, or adults of reproductive potential not employing an effective method of birth control. (Women of childbearing potential must have a negative serum pregnancy test within 48 hrs prior to administration of AMN107). Post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug
• Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)
• Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention.
• Patients unwilling or unable to comply with the protocol

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Tokyo, , Japan

Countries

Japan

References

Lange T, Ernst T, Gruber FX, Maier J, Cross M, Muller MC, Niederwieser D, Hochhaus A, Pfirrmann M. The quantitative level of T315I mutated BCR-ABL predicts for major molecular response to second-line nilotinib or dasatinib treatment in patients with chronic myeloid leukemia. Haematologica. 2013 May;98(5):714-7. doi: 10.3324/haematol.2012.068890. Epub 2012 Oct 12.

Reference Type: DERIVED

PMID: 23065514 (View on PubMed)

le Coutre P, Ottmann OG, Giles F, Kim DW, Cortes J, Gattermann N, Apperley JF, Larson RA, Abruzzese E, O'Brien SG, Kuliczkowski K, Hochhaus A, Mahon FX, Saglio G, Gobbi M, Kwong YL, Baccarani M, Hughes T, Martinelli G, Radich JP, Zheng M, Shou Y, Kantarjian H. Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia. Blood. 2008 Feb 15;111(4):1834-9. doi: 10.1182/blood-2007-04-083196. Epub 2007 Nov 29.

Reference Type: DERIVED

PMID: 18048643 (View on PubMed)

Related Links

https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=2952

Results for CAMN107A1101 can be found on the Novartis Clinical Trial Results Website

Other Identifiers

CAMN107A1101

Identifier Type: -

Identifier Source: org_study_id